The overall objective of this research is the isolation and characterization of mammalian cells, with particular reference to the purine de novo and salvage genes. We have noted that resistance to 2.6 diaminopure (DAP) occurs at a very high frequency (10 to the minus 3rd power) in mouse L-cells. These variants by a number of criteria appear to be true mutants. Although the majority of such mutants do not revert, one (TFS-9) reverts at a very high frequency. This reversion may be due to activation of a "silent allele", and such a model is currently being considered. Alpha-amanitin resistance also occurs at a high frequency in these cells, and the relationship of alpha-amR to DAPR will be investigated. As a byproduct of this work, azaserine resistant L-cells have been isolated. FGAR amidotransferase levels will be examined in these cells. We have isolated apt minus, gpt minus, and hpt minus mutants of E. Coli. hgt minus gpt minus double mutants give rise to purR mutants at a relatively high frequency. The mechanism of this selection for PurR minus mutant is under study.